[Immune, inflammatory, and nutritional protein profile in children with iron deficiency in Côte d'Ivoire]. / Déficit en fer, profil protéique immunitaire, inflammatoire et nutritionnel chez l'enfant de Côte-d'Ivoire.

Throughout the world and particularly in sub-Saharan Africa, deficiencies in trace elements constitute a real public health problem because of the insufficient nutritional quality of food. These trace elements are necessary for many of the body's biochemical reactions. The role of microelements such as vitamin A and zinc has been established in the functioning of the immune system and secretion of inflammatory reaction proteins, but the role of iron in these functions remains to be elucidated. The sample consists of 186 children (3/4) 80 with an iron deficiency and 106 with normal iron status. They range in age from 5 to 15 years and all attend school in the department of Adzope. The study excluded all children with parasites that might affect blood iron, protein and other hematological indicators, in particular, Plasmodium falciparum, Giardia intestinalis, Trichomonas intestinalis, Ascaris lumbricoides, and Ancylostoma. Inflammatory, immune and nutritional proteins were measured by radial immunodiffusion (Mancini's method). Ferritin was measured by a specific immunoenzymatic assay. Hematological indicators were tested by an automatic blood cell counter. Nutritional status was estimated by the weight/height ratio (W/H). This analysis showed that iron deficiency was associated with reduced IgG levels (p < 0.05), although immunoglobulins A and M remained stable (p > 0.05. Iron deficiency was also associated with reduced levels of thyroxine-binding prealbumin (TBPA) and albumin (p < 0.05). Inflammatory proteins did not differ significantly between the two groups (p > 0.05). Furthermore, the prognostic inflammatory and nutritional index (PINI) did not show any inflammatory, vital or nutritional risk, because it was lower than or equal to 2. Finally, malnutrition was not observed in the iron-deficient children: the difference in the weight/height ratio (W/H = 96.58 +/- 2.4%) between the children with iron deficiency and those with normal iron status (98.7 +/- 4.3%) did not differ significantly. The reduced IgG associated with iron deficiency may be attributed to the role that iron plays in the proliferation and maturation of lymphocytes. Reduced iron levels would thus lead to slowing down the hematopoietic mechanism, resulting in a decrease in B lymphocyte production and thus inevitably a reduction in IgG synthesis. The reduction in albumin and TBPA associated with the iron deficiency but in the absence of any sign of malnutrition (W/H > 96%) or inflammatory risk (PINI < 2) in either study group shows that iron may play a dominant role during protein synthesis. Iron deficiency might limit the energy of cellular tissues, leading to a reduction in RNA activity (transcription and translation), which would in turn decrease ribosome activity in tissues and thus reduce amino acid synthesis in cells, resulting in the reduction observed in protein synthesis. The lack of difference between the study groups in inflammatory proteins, notably CRP and alpha1-GPA, indicates that iron deficiency does not appear to be related to an inflammatory process. This study of children without any apparent clinical signs of iron deficiency shows that such a deficiency may be associated with a disruption in protein production. The proteins concerned include IgG, TBPA and albumin. The public authorities should pay particular attention to improving children's diets, especially their micronutrient levels, including for iron, vitamin A and zinc.

Hepatic extraction and renal production of 3,3'-diiodothyronine and 3',5'-diiodothyronine in man.

The sequential deiodination of thyroxine (T4) gives rise to several iodothyronine analogs including 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2). In vitro animal studies suggest that the liver and the kidneys are the main sites of both formation and degradation of 3,3'-T2 and 3',5'-T2. To determine the metabolism of 3,3'-T2 and 3',5'-T2 in human liver and kidneys plasma samples were obtained from (a) a brachial artery and a hepatic vein in 20 normal subjects, and from (b) a femoral artery and a renal vein in 11 normal subjects. Further, the hepatic plasma flow (a) and the renal plasma flow (b) were determined. Both plasma 3,3'-T2 and 3',5'-T2 levels were reduced in the hepatic venous blood as compared to arterial values (1.09 +/- 0.40 vs. 1.75 +/- 0.74 ng/dl (P < 0.02)) (mean +/- 1 SD). This resulted in a hepatic extraction of both, 3,3'-T2 and 3',5'-T2, which averaged 8.2 and 5.2 microgram/d, respectively. Plasma 3,3'-T2 as well as 3'5'-T2 levels were higher in the renal vein as compared to arterial values, 1.49 +/- 0.42 vs. 1.39 +/- 0.45 ng/dl (P < 0.05) and 2.35 +/- 0.83 vs. 2.09 +/- 0.81 ng/dl (P < 0.05), respectively. This positive venoarterial difference implies a net production of 3,3'-T2 and 3',5'-T2 in the kidneys of 1.2 and 3.0 microgram/d, respectively. It is concluded that the liver is an important site of 3,3'-T2 and 3',5'-T2 extraction in normal man. In contrast, the renal production of 3,3'-T2 as well as 3'5'-T2 exceeds the degradation and urinary excretion.

The distribution kinetics of triiodothyronine: studies of euthyroid subjects with decreased plasma thyroxine-binding globulin and patients with Graves' disease.

The kinetics of distribution of 3,3',5-triiodo-L-thyronine (T(3)) have been studied employing both a single-injection and a continuous infusion of T(3-) (131)I. External monitoring of radioactivity in the liver during the infusion permitted estimation of the hepatic distribution volume (V(H)) and the one-way hepatic clearance (C(H)) of the hormone. Among 10 euthyroid control subjects, V(H) averaged 2.07 liters +/-0.50 (SD), and the mean value for C(H), 231 ml of plasma per min (+/-64). In three euthyroid men whose plasma showed decreased binding capacity by thyroxine-binding globulin (TBG) abnormally high V(H) and C(H) values were found, the increase in C(H) being proportional to the decrease in binding activity by plasma proteins. Among all 13 subjects, there was a high correlation (+ 0.86) between C(H) and the proportion of free hormone in plasma, measured in vitro. In four patients with hyperthyroid Graves' disease V(H) ranged from 3.2 to 4.2 liters and C(H) was elevated in every case, averaging 989 ml/min. The increase in C(H) in this group was out of proportion to the elevation of free hormone fraction in plasma. Seven patients who were either euthyroid or hypothyroid after treatment of Graves' disease showed a slight but significant increase in C(H) compared with the euthyroid controls without Graves' disease. The percentage of free hormone in the plasma of the treated group was normal or low and therefore could not explain the persistent elevation in unidirectional hepatic clearance observed. The rate of accumulation of labeled T(3) in the tissues of the thigh during the interval from 10 to 60 min of the sustaining infusion of tracer was slow compared to the rate of equilibration in the liver and did not differ significantly among the various groups studied. These latter findings suggest that in slowly equilibrating tissues such as the thigh the kinetics of T(3) distribution are relatively insensitive to alterations in hormone-binding activity by plasma proteins.

Studies on human thyroxine-binding globulin. VI. The nature of slow thyroxine-binding globulin.

A model system utilizing a highly purified partially desialylated thyroxine-(T(4)) binding protein (STBG) was studied. STBG was prepared by the same affinity chromatographic method we have reported for preparation of highly purified T(4)-binding globulin (TBG). The necessary prerequisite for preparation of STBG was the use of T(4)-substituted Sepharose which had been repeatedly exposed to large volumes of serum for purification of TBG. STBG moved more slowly on cellulose acetate electrophoresis than TBG but had the same molecular weight and antigenic determinants as TBG. It bound T(4) with a 1: 1 molar ratio but its affinity for T(4) was about 10 times less than that of TB. STBG had about onefourth the sialic acid content of TBG and the electrophoretic mobility of this protein was similar to that of a T(4)-binding protein with a mobility slower than that of TBG which has been seen in the electrophoretic patterns of some normal human serums and in serums of patients with hepatic cirrhosis and which does not appear to be an artifact caused by storage and freezing of serum. This fourth slowly migrating T(4)-binding region in electrophoretograms of cirrhotic serums is completely abolished by prior incubation with rabbit antiserum to TBG. The in vitro production of partially desialylated TBG from T(4)-Sepharose which had been previously exposed to large volumes of serum may be due to adsorption of neuraminidases to the Sepharose either directly from serum or as the result of bacterial contamination. Partial desialylation of TBG in vivo may be an early step in the catabolism of this protein.

Estimation of rapidly exchangeable cellular thyroxine from the plasma disappearance curves of simultaneously administered thyroxine-131-I and albumin-125-I.

A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-(131)I and albumin-(125)I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-(125)I can be used to represent the expansion of the thyroxine-(131)I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-(131)I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-(131)I and albumin-(125)I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-(131)I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation.

Studies on human thyroxine-binding globulin (TBG). I. Purification of TBG and immunologic studies on the relationship between TBG from normal persons and those with TBG "deficiency".

A method for obtaining highly purified thyroxine-binding globulin (TBG) from whole human serum is presented. The method employs relatively simple procedures of step-wise ammonium sulfate precipitation followed by column chromatography on DEAE cellulose and DEAE Sephadex. The final product produces a single protein band on disc electrophoresis. The sedimentation constant of the TBG thus purified is 3.91 and its calculated mol wt is 54,000. An antiserum to the highly purified TBG produced a single arc on immunoelectrophoresis. When the antiserum was reacted against normal human serum or against serum from subjects deficient in TBG, each produced two arcs-one identical with that produced by the antigen alone. The second arc is probably the result of a contaminating protein in the antigen, present in too low a concentration to be detectable by disc gel electrophoresis. It is concluded that some persons with TBG "deficiency" have a circulating protein, immunologically indistinguishable from TBG, which is defective in its ability to bind thyroxine.

Study of four new kindreds with inherited thyroxine-binding globulin abnormalities. Possible mutations of a single gene locus.

Five families with inherited thyroxine-binding globulin (TBG) abnormalities were studied. On the basis of serum thyroxine (T(4))- binding capacity of TBG in affected males, three family types were identified: TBG deficiency, low TBG, and high TBG capacity. In all families evidence for X-linked inheritance was obtained and in one family all criteria establishing this mode of inheritance were met. Only females were heterozygous, exhibiting values intermediate between affected males and normals. Overlap in heterozygotes was most commonly encountered in families with low TBG. QUANTITATIVE VARIATION IN THE SERUM CONCENTRATION OF FUNCTIONALLY NORMAL TBG WAS DEMONSTRATED BY: (a) failure of serum from TBG-deficient subjects to react with anti-TBG antibodies; (b) normal kinetics of T(4) and triiodothyronine-binding to TBG in sera from subjects with low TBG and high TBG capacity; (c) concordance of estimates of TBG concentration by T(4) saturation and by immunological methods; and (d) normal rate of heat inactivation of TBG. No abnormalities in serum transport of cortisol, testosterone, aldosterone, or thyroxine bound to prealbumin could be detected. These observations suggest that all the TBG abnormalities thus far observed reflect mutations at a single X-linked locus involved in the control of TBG synthesis.

Studies on human thyroxine-binding globulin (TBG). IX. Some physical, chemical, and biological properties of radioiodinated TBG and partially desialylated TBG.

Thyroxine-binding globulin (TBG) and partially desialylated or slow TBG (STBG) were purified from human serum by affinity chromatography. Purified TBG was identical to TBG present in serum by the criteria of electrophoretic mobility, affinity for thyroxine (T4), and heat-inactivation response. Purified STBG had slower electrophoretic mobility and lower affinity for T4. Both bound T4 in an equimolar ratio, were immunoprecipitable, and had similar inactivation t1/2 at 61 degrees C. TBG and STBG were iodinated by the chloramine-T-catalyzed reaction. An average of from 0.02 to 6 atoms I could be incorporated per molecule of the protein by adjusting the conditions of the reaction (time, protein and iodide concentrations). 125-I, 131-I, and 127-I were used. Iodination increased the anodal mobility of TBG but did not affect the reversible T4-binding, precipitation by antiserum, or the heat-inactivation properties. "Heavily" and "lightly" iodinated TBG had identical disappearance half-times from serum in the rabbit. 15 min after the intravenous administration of [131-I]-STBG and [125-I]TBG mixture to rats, more than 90% of the injected 131-I dose was in the liver, and the liver 131-I/125-I ratio was 32-fold that of serum. Selective uptake of STBG by the liver was also observed in the rabbit and in man. The serum [125-I]STBG/[131-I]TBG ratio declined from 1 to 0.2 in 10 min in the intact rabbit but remained unchanged for 1 h in the acutely hepatectomized animal. In the rabbit, t 1/2 was approximately 3 min for STBG and 0.8-3.4 days for TBG. The radioiodine derived from the iodinated proteins is partly excreted in bile but the bulk was precipitable with specific antibodies. Some isotope in the form of iodide appeared in blood and was excreted in the urine. Since radioiodinated TBG and STBG preserve their biologic and immunologic properties they are useful as tracer materials for metabolic studies. In rat, rabbit, and man STBG is rapidly cleared from serum by the liver. Conversion of TBG to STBG may be the limiting step in the regulation of TBG metabolism.

Alterations in thyroid hormone economy in patients with hydatidiform mole.

Studies of several aspects of thyroid hormone economy have been conducted in 11 patients before and after removal of a molar pregnancy. Before evacuation of the mole, all patients demonstrated moderately to greatly elevated values for thyroidal (131)I uptake, absolute iodine uptake, and serum protein-bound-(131)I. Values for serum PBI and serum thyroxine (T(4)) concentration were consistently and often greatly increased, averaging more than twice those found in normal pregnancy and three times those in normal controls. On the other hand, the maximum binding capacity of the T(4)-binding globulin (TBG) was variably affected, and ranged between the values found in normal controls and those found in normal pregnancy. Values for the absolute concentration of free T(4) in serum were, on the average, only moderately elevated, since the proportion of free T(4) was moderately low, although not as low as in normal pregnancy. Sera of patients with molar pregnancy contained high levels of thyroid stimulating activity, as assessed in the McKenzie mouse bioassay system. The stimulator displayed a more prolonged duration of action than that of TSH and did not reveal a major immunological cross-reactivity with either human or bovine TSH, differing in the latter respect from the chorionic thyrotropin of normal human placenta. Abnormalities in iodine metabolism were rapidly ameliorated after removal of the molar pregnancy, and this was associated with the disappearance from serum of the thyroid stimulator. Despite the foregoing evidence of thyroid hyperfunction and hypersecretion of T(4), patients with molar pregnancy were neither goitrous nor overtly thyrotoxic. They did display, however, high values of the urinary pigment/creatinine ratio, a possible indication of the presence of a hypermetabolic state. It is concluded that in patients with molar pregnancy, thyroid function and T(4) secretion are stimulated, often greatly so, by an unusual thyroid stimulator which is demonstrable in the blood and which is probably of molar origin. The nature of the stimulator, as well as the reasons for both the variability of the increase in TBG which occurs in molar pregnancy and the lack of frank thyrotoxicosis, remain to be clarified.

The effect of diphenylhydantoin on thyroxine metabolism in man.

The effect of 5,5'-diphenylhydantoin on thyroxine metabolism was examined in five normal volunteers. Intravenous injection of radiothyroxine was followed by a 10-12 day control and subsequent 9-14 day treatment periods. During oral administration of diphenylhydantoin, plasma thyroxine concentration decreased to about 80% of its pretreatment level and the plasma radiothyroxine disappearance rate increased a maximum of 20% over control estimates. These changes were a result of increases in both urinary and fecal excretion of radioisotope.A minimum plasma thyroxine was apparent after 10-12 days of diphenylhydantoin administration. In two of the subjects, treatment was sufficiently prolonged to achieve this new steady state. In these subjects, the decrease in total body thyroxine was balanced by the increase in the fractional turnover rate. As a result, absolute thyroxine degradation during diphenylhydantoin administration was unchanged from the pretreatment values. Plasma ultrafiltration was used to estimate the free thyroxine fraction at regular intervals during the control and treatment periods. During diphenylhydantoin treatment, there was little or no change in this fraction and therefore, absolute free thyroxine decreased. Thyroxine-binding globulin and thyroxine-binding prealbumin capacities remained constant. These results indicate that thyroxine degradation can proceed at a normal rate in subjects receiving diphenylhydantoin despite decreases in plasma free thyroxine concentration. If free thyroxine is the only portion of the hormone available for cellular utilization, then free thyroxine clearance must be increased in these subjects. This increase in clearance could represent either a direct stimulation of peripheral thyroxine metabolism by diphenylhydantoin, or it could reflect the response of intrinsic regulatory systems to a diphenylhydantoin-mediated displacement of thyroxine from thyroxine-binding globulin. Whatever the mechanism for this effect, a decreased free thyroxine value in patients receiving diphenylhydantoin may not imply hypothyroidism.

Impact of varying levels of protein intake on protein status indicators after gastric bypass in patients with multiple complications requiring nutritional support.

BACKGROUND: <6% of patients who undergo Roux-en-Y gastric bypass (RYGBP) for morbid obesity require nutritional support after surgery. Protein and caloric needs have been estimated as 14-21 kcal, 1.2 g protein/kg/current body weight/day in uncomplicated morbidly obese patients. This study assesses the effect of varying protein-calorie intake in complicated patients after RYGBP on two markers of protein status: thyroxine-binding prealbumin (TBPA) and serum albumin. METHODS: This 25-month retrospective study consisted of 22 patients with postoperative complications. Serum albumin, TBPA, medical nutrition care-plans, laboratory data and history were reviewed. These post-RYGBP patients who had BMI>35 and no multi-system organ failure or fistulas, had complications after surgery requiring nutrition support services (NSS). Serum albumin and TBPA were matched to fed levels of protein using random coefficient regression analysis. RESULTS: Mean incremental increases of 2.34 mg/dl (TBPA, P=0.0113) and 0.11 g/dl (serum albumin, P=0.0272) were found with each 0.5 g protein intake increase/kg ideal body weight/day (kg/IBW/day). Patients required NSS for 23+/-21 (mean+/-SD) days, with 15+/-19 days fed at goal rate. Initial serum albumin was 2.3+/-0.5, with a final measure of 2.7+/-0.5 g/dl. Goal protein and calorie intake were 2.1 g and 17 kcal/kg IBW/day versus actual intake of 1.6 g and 13 kcal/kg IBW/day. CONCLUSION: Morbidly obese patients requiring NSS following RYGBP risk iatrogenic protein malnutrition. There was a positive linear relationship between protein status and protein intake that warrants further study of higher protein feeding in complicated post-RYGBP patients.

Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic proteins.

OBJECTIVE: The purpose of this study was to evaluate the effects of the contraceptive patch and an oral contraceptive (OC) on serum concentrations of estrogen-sensitive hepatic proteins, ethinyl estradiol (EE) and levonorgestrel (LNG). METHODS: Twenty-four women were randomized to receive three cycles of a contraceptive patch that delivers EE 20 microg/day and norelgestromin 150 microg/day or an OC that contains EE 35 microg and norgestimate 250 microg. Blood samples were taken at baseline and at the end of Cycle 3. Serum levels of sex-hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG), corticosteroid-binding globulin (CBG) and C-reactive protein (CRP) were quantified by immunoassay methods. EE and LNG levels in patch users were measured by radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The paired t test and Student's t test were used for statistical analysis. RESULTS: Nineteen women completed the study (patch, n=10; OC, n=9). Treatment with both the patch and OC resulted in significant increases from baseline in SHBG, TBG and CBG. The increase in CRP was significant in the patch group and approached significance in the OC group. The increases in SHBG and TBG observed with the patch were significantly greater than those associated with the OC. By way of RIA and LC-MS/MS assay methods, the patch was associated with mean EE levels of 114 and 111 pg/mL, respectively. CONCLUSIONS: The serum concentrations of estrogen-sensitive hepatic proteins and EE associated with the patch suggest that this new contraceptive system may have relatively large net estrogen effects.

Congenital hypothyroidism and the second newborn metabolic screening in Colorado, USA.

OBJECTIVE: To evaluate the effectiveness of a second newborn screening for congenital hypothyroidism (CH). METHODS: All infants born in Colorado, USA, from July 1996 through June 2004 had a total thyroxine measured with secondary thyroid stimulating hormone determination. RESULTS: The number of first and second newborn screens completed was 494,324 and 471,877, respectively. The first screen identified 185 cases of CH (incidence of 1:2,703). The second screen identified an additional 42 cases. Overall, the incidence based on both the first and second screenings was 1:2,174. The false negative rate for the first screen was 15.6%. In the absence of a second screen, one infant with CH out of every 11,111 babies screened would have been missed. The addition of the second screen increased the cost-per-case identified from dollars 6,108 to dollars 9,730. CONCLUSIONS: With only one newborn screen for CH, the number of missed cases is significant and higher than previously reported.

Role of sialic acid in the microheterogeneity of serum thyroxine-binding globulin. Study by two-dimensional isoelectric focusing.

A new technique combining a neuraminidase treatment of thyroxine-binding globulin after serum isoelectric focusing and a second-dimensional isoelectric focusing was developed to study the role of sialic acid in the microheterogeneity of native thyroxine-binding globulin. By showing the change of PI occasioned by the desialylation for each of the bands constituting the thyroxine-binding globulin pattern separately, this procedure clearly demonstrated that the microheterogeneity of the native protein could not be imputed to the varying sialic acid content of the bands only. We suggest that at least three molecules of thyroxine-binding globulin, with probably slight differences in their amino acid composition, are present in the serum, and that different degrees of sialylation ensure greater microheterogeneity of this protein.

Elevation of serum free triiodothyronine, total triiodothyronine, thyroxine-binding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder.

BACKGROUND: This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work. METHODS: A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin. RESULTS: The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups. CONCLUSIONS: These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.

Hypothyroxinemia in cardiac arrest.

Thyroid function was evaluated in cardiac arrest (CA), a condition associated with marked activation of the pituitary-adrenal axis. Blood samples were obtained in 24 patients immediately after diagnosis of CA and again ten minutes later. Samples were also obtained from 22 patients admitted consecutively to the intensive care unit (ICU). Abnormalities of thyroid indexes among patients on the ICU who had not experienced CA were low triiodothyronine (T3) in 45%, low thyroxine (T4) in 32%, low free T4 (equilibrium dialysis) in 21%, and elevated reverse T3 levels in 36%. The alterations of thyroid values were both more common and marked in patients with CA, with abnormally low T3 in 84% of the patients, low T4 in 65%, low free T4 in 65%, and high reverse T3 in 80%. Thyroxine-binding globulin and prealbumin concentrations were below the normal range in 40% and 21% of patients with CA. A thyroid hormone-binding inhibitor was detected in 38% of patients with CA. Thyroglobulin level was slightly high in patients with CA but not significantly different from controls on the ICU. The abnormalities present at zero minutes were further exaggerated ten minutes after CA. We conclude that abnormalities on tests measuring thyroid function are extremely common during the cardiovascular emergency of CA.

Abnormalities in thyroid function tests in patients admitted to medical service.

Serum thyroid hormone, thyrotropin (TSH) and thyroxine-binding globulin (TBG) concentrations, free thyroxine index values, and free thyroxine concentrations were measured at the time of admission in all 77 patients hospitalized on a medical service on four separate days. Serum thyroxine (T4) concentrations and serum free T4 index values were decreased in 19.5% and 11.7%, respectively, and increased in 3.9% and 11.7%, respectively; serum free T4 concentrations were decreased in 6.8% and increased in 5.4%. Six patients (7.8%) had increased serum TSH concentrations. Serum triiodothyronine (T3) concentrations were decreased in 26.0% and reverse triiodothyronine (rT3) concentrations were increased in 29.9%. None had manifestations of thyroid disease. These results indicate that available thyroid function tests may give misleading results in patients with nonthyroid illness and suggest that caution be exercised in diagnosing thyroid disease in hospitalized patients.

Plasma thyronine levels in carcinoma of the breast and colon.

Plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), total thyroid hormone-binding globulin (TBG) capacity, and serum albumin were assayed in patients with early and advanced breast and colonic cancer and in healthy women. Plasma T3 levels were reduced in both breast cancer group, but were reduced only in colonic cancer patients with systemic metastases. Plasma rT3 was normal in early cancer, but increased in nine of 38 (24%) with advanced breast cancer and four of 17 (24%) with metastatic colonic cancer; in consequence their rT3/T3 ratios were elevated. Plasma T4 concentrations were normal in all patient groups. Plasma TBG capacity was reduced in breast cancer patients with systemic metastases and a similar tendency occurred in metastatic colonic cancer. Levels of TBG were positively correlated with the serum albumin values. These changes were associated particularly with liver metastases.

Clinical significance of low serum thyrotropin concentration by chemiluminometric assay in 85-year-old women and men.

The prevalence and causes of low serum thyrotropin concentration were studied in 886 individuals at age 85 years (601 women and 285 men). All participants were subject to detailed clinical and biochemical evaluation, including determination of serum thyrotropin and free thyroxine concentrations by chemiluminometric assays. Samples with thyrotropin concentrations below 0.20 mU/L or above 6.0 mU/L and/or free thryoxine concentrations above 22.0 pmol/L were selected for further assays. These selected individuals were followed-up during 3 years. Of 18 individuals without thyroid hormone treatment who had thyrotropin concentrations less than 0.20 pmol/L (13 below 0.10 pmol/L), only two were proved to be hyperthyroid; in another three, hyperthyroidism could not be excluded. The results indicate that most elderly individuals with low serum thyrotropin concentrations are not hyperthyroid and that abnormal thyroxine-binding globulin (in conjunction with drug treatment or nonthyroidal illness) is not a common cause of low thyrotropin concentration.